title: Effects of repeated allopurinol administration on rat cytochrome P450 activity.
abstract: Allopurinol is a popular and widely-prescribed anti-hyperuricemic agent that has been implicated in drug interactions with substrates of several cytochrome P450 (CYP) enzymes. The effect of repeated allopurinol administration (20 mg/kg, once daily for 14 days) on metabolic activity of CYP was assessed in rats. This was a randomized, double-blind, two-way crossover study with a 4-week washout period between phases. The substrates used in this study were phenacetin (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19) and dextromethorphan (CYP2D6). Validated HPLC-MS/MS was used to quantify all compounds. Our study showed that allopurinol administration inhibited CYP1A2 activity, causing a significant increase in AUC (0-infinity) (P < 0.01) and t1/2 (P < 0.05) of phenacetin, and a distinct decline in CL (P < 0.01). However, there were no significant differences of another three probe drugs in plasma concentrations and the corresponding pharmacokinetic parameters between the allopurinol-treated and normal saline-treated rats. The findings in this study suggested that allopurinol could inhibit CYP1A2 but did not influence CYP2C9, CYP2C19 and CYP2D6 enzymes.
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
authors.forename: Ren-Ai
authors.initials: RA
authors.lastname: Xu
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Xu
authors.forename: Lu-Feng
authors.initials: LF
authors.lastname: Hu
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Zhang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Pan
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Shi
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Ye
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Llu
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006207:Half-Life; D007202:Indicators and Reagents; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D000493:Allopurinol; D003577:Cytochrome P-450 Enzyme System